01925nas a2200253 4500008004100000022001400041245011500055210006900170260000800239300000900247490000700256520106700263100001801330700001901348700002301367700002201390700002301412700001901435700001801454700001901472700002801491700002401519856012801543 2020 eng d a2041-172300aDistinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis0 aDistinct metabolic states of a cell guide alternate fates of mut cJUN a29260 v113 a
Metabolic changes alter the cellular milieu; can this also change intracellular protein folding? Since proteostasis can modulate mutational buffering, if change in metabolism has the ability to change protein folding, arguably, it should also alter mutational buffering. Here we find that altered cellular metabolic states in E. coli buffer distinct mutations on model proteins. Buffered-mutants have folding problems in vivo and are differently chaperoned in different metabolic states. Notably, this assistance is dependent upon the metabolites and not on the increase in canonical chaperone machineries. Being able to reconstitute the folding assistance afforded by metabolites in vitro, we propose that changes in metabolite concentrations have the potential to alter protein folding capacity. Collectively, we unravel that the metabolite pools are bona fide members of proteostasis and aid in mutational buffering. Given the plasticity in cellular metabolism, we posit that metabolic alterations may play an important role in cellular proteostasis.
1 aVerma, Kanika1 aSaxena, Kanika1 aDonaka, Rajashekar1 aChaphalkar, Aseem1 aRai, Manish, Kumar1 aShukla, Anurag1 aZaidi, Zainab1 aDandage, Rohan1 aShanmugam, Dhanasekaran1 aChakraborty, Kausik uhttp://library.ncl.res.in/content/distinct-metabolic-states-cell-guide-alternate-fates-mutational-buffering-through-altered